Breast cancer is a major public health problem. The identification of new markers to differentiate neoplastic from the normal cells, more thorough understanding of different stages of the pathology, as well as the definition of new therapeutic targets, are all of critical importance. With the completion of human genome sequencing and the introduction of mass spectrometry, combined with protein identification via advanced bioinformatics, proteomics has emerged as a valuable tool for the discovery of new molecular markers. New methods in functional proteomics have also been developed to study the intracellular signaling pathways that underline the development of breast cancer. As illustrated with the examples of fibroblast growth factor-2 and H19, an oncogenic, noncoding mRNA, proteomics have become a powerful approach for deciphering the complex signaling circuitry involved in tumor growth. Breast cancer proteomics have already identified proteins of potential clinical interest (such as the molecular chaperone 14-3-3 sigma) and technological innovations in large scale/high throughput analysis are now ushering in new prospects.